Regulation of Blood Flow in the Retinal Trilaminar Vascular Network

Kornfield, Tess E.; Newman, Eric A.

doi:10.1523/jneurosci.1971-14.2014

Cited by 162 publications

(195 citation statements)

References 59 publications

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“…Specifically, Kornfield et al 22 observed 11% increase in the superficial RBF following 2-second flicker stimulation by using functional MRI (BOLD), which compares well with the~10% increase we measured with DOCT for flicker stimulus of the same duration. Radhakrishnan et al 23 reported~12% blood flow increase for a 10-second flicker stimulus using en-face Doppler OCT, while Werkmeister et al 24 detected over 30% increase of blood flow with 60-second flicker stimulus using DOCT.…”

Section: Discussionsupporting

confidence: 87%

Correlation of Visually Evoked Functional and Blood Flow Changes in the Rat Retina Measured With a Combined OCT+ERG System

Tan

Mason

MacLellan

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. To correlate visually evoked functional and blood flow changes in the rat retina measured simultaneously with a combined optical coherence tomography and electroretinography system (OCTþERG).METHODS. Male Brown Norway (n ¼ 6) rats were dark adapted and anesthetized with ketamine/xylazine. Visually evoked changes in the retinal blood flow (RBF) and functional response were measured simultaneously with an OCTþERG system with 3-lm axial resolution in retinal tissue and 47-kHz image acquisition rate. Both single flash (10 and 200 ms) and flicker (10 Hz, 20% duty cycle, 1-and 2-second duration) stimuli were projected onto the retina with a custom visual stimulator, integrated into the OCT imaging probe. Total axial RBF was calculated from circular Doppler OCT scans by integrating over the arterial and venal flow.RESULTS. Temporary increase in the RBF was observed with the 10-and 200-ms continuous stimuli (~1% and~4% maximum RBF change, respectively) and the 10-Hz flicker stimuli (~8% for 1-second duration and~10% for 2-second duration). Doubling the flicker stimulus duration resulted in~25% increase in the RBF peak magnitude with no significant change in the peak latency. Single flash (200 ms) and flicker (10 Hz, 1 second) stimuli of the same illumination intensity and photon flux resulted in~23 larger peak RBF magnitude and~25% larger RBF peak latency for the flicker stimulus.CONCLUSIONS. Short, single flash and flicker stimuli evoked measureable RBF changes with larger RBF magnitude and peak latency observed for the flicker stimuli.

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Section: Discussionsupporting

confidence: 87%

Correlation of Visually Evoked Functional and Blood Flow Changes in the Rat Retina Measured With a Combined OCT+ERG System

Tan

Mason

MacLellan

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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“…Offline, a software package (NIS Elements version 4.0) facilitated the lumen measurements used to calculate the change in mean diameter during exposure to experimental solutions. Of note, similar to in vivo observations (32), changes in lumen diameter of arterioles in ex vivo retinas were not uniform along a vessel; this study used the maximal change detected within the well-focused portion (∼25-μm long) of a monitored vessel.…”

Section: Methodsmentioning

confidence: 70%

Bioelectric impact of pathological angiogenesis on vascular function

Puro

Kohmoto

Fujita

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Pathological angiogenesis, as seen in many inflammatory, immune, malignant, and ischemic disorders, remains an immense health burden despite new molecular therapies. It is likely that further therapeutic progress requires a better understanding of neovascular pathophysiology. Surprisingly, even though transmembrane voltage is well known to regulate vascular function, no previous bioelectric analysis of pathological angiogenesis has been reported. Using the perforated-patch technique to measure vascular voltages in human retinal neovascular specimens and rodent models of retinal neovascularization, we discovered that pathological neovessels generate extraordinarily high voltage. Electrophysiological experiments demonstrated that voltage from aberrantly located preretinal neovascular complexes is transmitted into the intraretinal vascular network. With extensive neovascularization, this voltage input is substantial and boosts the membrane potential of intraretinal blood vessels to a suprahyperpolarized level. Coincident with this suprahyperpolarization, the vasomotor response to hypoxia is fundamentally altered. Instead of the compensatory dilation observed in the normal retina, arterioles constrict in response to an oxygen deficiency. This anomalous vasoconstriction, which would potentiate hypoxia, raises the possibility that the bioelectric impact of neovascularization on vascular function is a previously unappreciated pathophysiological mechanism to sustain hypoxia-driven angiogenesis.neovascularization | proliferative retinopathy | retinopathy of prematurity | proliferative diabetic retinopathy | retina T he abnormal growth of blood vessels is a key pathophysiological feature of numerous disorders, including tumorigenesis, arthritis, endometriosis, and retinopathies. Despite substantial progress from studies of patients and animal models, abnormal neovascularization remains a common threat to health and wellbeing. To help address this challenge, we devised a unique experimental approach to better understand neovascular pathophysiology. Because almost nothing is known about the electrogenic profile of neovascular complexes and how these complexes functionally interact with their parent vessels, we focused on the bioelectric features of neovascularization. These gaps in knowledge are surprising, considering that it is well established that the transmembrane voltage of vascular cells (1), as well as electrotonic cell-cell interactions within a vascular network (2-4), play vital roles in regulating blood flow.In this electrophysiological analysis of pathological angiogenesis, we focused on abnormal vasoproliferation in rodent and human retinas. For multiple reasons, the retina is an ideal tissue for this undertaking. First is its clinical importance. Retinal vasoproliferation is the major cause of blindness in prematurely born infants (retinopathy of prematurity) and persons with diabetes (proliferative diabetic retinopathy) and sickle cell disease (sickle cell retinopathy). The hallmark of these disorders is abno...

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“…Rat experiments indicate that flicker stimulation evokes larger dilations in the intermediate layer capillaries than in the superficial and deep layer capillaries. 55 Recently, Duan et al 56 reported a vasodilation of 13% 6 5% in the precapillary arterioles, 31% 6 8% in the capillaries, and 10% 6 3% in the postcapillary venules by using adaptive optics imaging in the human retina while applying focal patches of flickering visible light. For the above reasons, although showing a clear trend, the increases in the power fit exponents as calculated by the model are lower than the ones observed in vivo.…”

Section: Discussionmentioning

confidence: 99%

Effect of Diffuse Luminance Flicker Light Stimulation on Total Retinal Blood Flow Assessed With Dual-Beam Bidirectional Doppler OCT

Aschinger

Schmetterer

Fondi

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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METHODS. In six healthy subjects, TRBF was measured before and during stimulation with diffuse luminance flicker. Blood flow velocities in retinal vessels were measured via dual-beam bidirectional Doppler Fourier-domain optical coherence tomography (FD-OCT), retinal vessel diameters were assessed based on FD-OCT phase data. This allowed for the calculation of TRBF before and during visual stimulation. Additionally, a mathematical flow model for the retinal vasculature was adapted to study the implications of diameter variations on retinal perfusion. Measured and simulated perfusion was compared to draw conclusions on the diameter variations in different layers of the vascular tree.RESULTS. The measured mean baseline flow was 36.4 6 6.5 ll/min while the mean flow during flicker stimulation was 53.4% 6 8.3 ll/min. The individual increase in TRBF during flicker stimulation ranged between 34% and 66%. The average increase in TRBF over all measured subjects was 47.6% 6 12.6%.CONCLUSIONS. Dual-beam bidirectional Doppler FD-OCT allowed quantifying NC in the human retina in vivo and may be a promising method for monitoring alterations in NC caused by various pathologies. The comparison of the measured data with the results obtained in the simulated vasculature indicates that the vasodilation induced by NC is more pronounced in smaller vessels.

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Regulation of Blood Flow in the Retinal Trilaminar Vascular Network

Cited by 162 publications

References 59 publications

Correlation of Visually Evoked Functional and Blood Flow Changes in the Rat Retina Measured With a Combined OCT+ERG System

Correlation of Visually Evoked Functional and Blood Flow Changes in the Rat Retina Measured With a Combined OCT+ERG System

Bioelectric impact of pathological angiogenesis on vascular function

Effect of Diffuse Luminance Flicker Light Stimulation on Total Retinal Blood Flow Assessed With Dual-Beam Bidirectional Doppler OCT

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